rs121908120

Positions:

chr2-218890289-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PP3PP5BP4BS1_Supporting

The NM_025216.3(WNT10A):c.682T>A(p.Phe228Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0208 in 1,608,024 control chromosomes in the GnomAD database, including 449 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.014 ( 22 hom., cov: 32)

Exomes 𝑓: 0.021 ( 427 hom. )

Consequence

WNT10A
NM_025216.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:23U:1O:3

Conservation

PhyloP100: 7.94

Variant links:

Genes affected

WNT10A (HGNC:13829): (Wnt family member 10A) The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. It is strongly expressed in the cell lines of promyelocytic leukemia and Burkitt's lymphoma. In addition, it and another family member, the WNT6 gene, are strongly coexpressed in colorectal cancer cell lines. The gene overexpression may play key roles in carcinogenesis through activation of the WNT-beta-catenin-TCF signaling pathway. This gene and the WNT6 gene are clustered in the chromosome 2q35 region. [provided by RefSeq, Jul 2008]

WNT10A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 9: AlphaMissense, BayesDel_noAF, Cadd, Eigen, MutationAssessor, phyloP100way_vertebrate, PrimateAI, PROVEAN, REVEL [when BayesDel_addAF, max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

PP5

Variant 2-218890289-T-A is Pathogenic according to our data. Variant chr2-218890289-T-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 4462.We mark this variant Likely_pathogenic, oryginal submissions are: {Pathogenic_low_penetrance=1, Likely_pathogenic=2, not_provided=3, Uncertain_significance=1, Pathogenic=15}. Variant chr2-218890289-T-A is described in Lovd as [Pathogenic]. Variant chr2-218890289-T-A is described in Lovd as [Likely_pathogenic]. Variant chr2-218890289-T-A is described in Lovd as [Pathogenic]. Variant chr2-218890289-T-A is described in Lovd as [Pathogenic].

BP4

Computational evidence support a benign effect (MetaRNN=0.013546854). . Strength limited to SUPPORTING due to the PP5.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.014 (2138/152210) while in subpopulation NFE AF= 0.0223 (1515/67990). AF 95% confidence interval is 0.0213. There are 22 homozygotes in gnomad4. There are 934 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
WNT10A	NM_025216.3 linkuse as main transcript	c.682T>A	p.Phe228Ile	missense_variant	3/4	ENST00000258411.8	NP_079492.2
WNT10A	XM_011511929.3 linkuse as main transcript	c.586T>A	p.Phe196Ile	missense_variant	4/5		XP_011510231.1
WNT10A	XM_011511930.2 linkuse as main transcript	c.377-2485T>A		intron_variant			XP_011510232.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNT10A	ENST00000258411.8 linkuse as main transcript	c.682T>A	p.Phe228Ile	missense_variant	3/4	1	NM_025216.3	ENSP00000258411	P1
WNT10A	ENST00000458582.1 linkuse as main transcript	c.264-2485T>A		intron_variant		3		ENSP00000388812

Frequencies

GnomAD3 genomes

AF:

0.0141

AC:

2138

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00408

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0156

Gnomad ASJ

AF:

0.0346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00424

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0223

Gnomad OTH

AF:

0.0148

GnomAD3 exomes

AF:

0.0139

AC:

3389

AN:

243534

Hom.:

AF XY:

0.0140

AC XY:

1852

AN XY:

132646

show subpopulations

Gnomad AFR exome

AF:

0.00372

Gnomad AMR exome

AF:

0.0106

Gnomad ASJ exome

AF:

0.0349

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00167

Gnomad FIN exome

AF:

0.00470

Gnomad NFE exome

AF:

0.0213

Gnomad OTH exome

AF:

0.0163

GnomAD4 exome

AF:

0.0215

AC:

31289

AN:

1455814

Hom.:

427

Cov.:

AF XY:

0.0212

AC XY:

15348

AN XY:

724498

show subpopulations

Gnomad4 AFR exome

AF:

0.00358

Gnomad4 AMR exome

AF:

0.0113

Gnomad4 ASJ exome

AF:

0.0353

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00186

Gnomad4 FIN exome

AF:

0.00531

Gnomad4 NFE exome

AF:

0.0254

Gnomad4 OTH exome

AF:

0.0172

GnomAD4 genome

AF:

0.0140

AC:

2138

AN:

152210

Hom.:

Cov.:

AF XY:

0.0125

AC XY:

934

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00407

Gnomad4 AMR

AF:

0.0156

Gnomad4 ASJ

AF:

0.0346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00424

Gnomad4 NFE

AF:

0.0223

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.0225

Hom.:

Bravo

AF:

0.0146

TwinsUK

AF:

0.0262

AC:

ALSPAC

AF:

0.0249

AC:

ESP6500AA

AF:

0.00727

AC:

ESP6500EA

AF:

0.0243

AC:

209

ExAC

AF:

0.0125

AC:

1517

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:23Uncertain:1Other:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Pathogenic:5

Likely pathogenic, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Pathogenic, no assertion criteria provided	clinical testing	Molecular Genetics laboratory, Necker Hospital	Apr 15, 2021	- -
Pathogenic, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Oct 07, 2022	The WNT10A c.682T>A (p.Phe228Ile) missense variant results in the substitution of phenylalanine at amino acid position 228 with isoleucine. This variant is one of the most commonly reported WNT10A variants associated with hypodontia and ectodermal dysplasia. Across a selection of the available literature, the c.682T>A variant has been reported in a homozygous state in 12 unrelated affected individuals, in a compound heterozygous state in 11, and in a heterozygous state in six (PMID: 22581971; PMID: 28105635). It has also been shown to co-segregate with the phenotype with reduced penetrance in multiple families (PMID: 30426266). The highest frequency of this allele in the Genome Aggregation Database is 0.03482 in the Ashkenazi Jewish population (version 2.2.1). In the total population, it is reported in a homozygous state in 42 individuals. This frequency is high but consistent with the reduced penetrance demonstrated for the variant and the prevalence and variable expressivity of the disease. A case-control study of over 2000 individuals found the c.682T>A variant conferred a 3.25-fold increased risk for isolated tooth agenesis (95% CI: 2.74-3.85) (PMID: 29364747). This variant is located in the Wnt domain, in a region implicated in interactions with Frizzled and thus intracellular Wnt signaling (PMID: 28105635), and is predicted to affect protein function by computational algorithms. Based on the available evidence, the c.682T>A (p.Phe228Ile) variant is classified as pathogenic for WNT10A-related disorders. -
Pathogenic, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	WNT10A: PM3:Very Strong, PP1:Strong, PM2:Supporting, PP3 -
Pathogenic, criteria provided, single submitter	clinical testing	GeneDx	Jul 27, 2020	One of the most common pathogenic variants reported in this gene associated with semi-dominant ectodermal dysplasia with variable expressivity; Observed in the heterozygous state in individuals with isolated hypodontia or oligodontia, in individuals with other features of ectodermal dysplasia, and also in unaffected carriers (Bohring et al., 2009; Kantaputra et al., 2011; Cluzeau et al., 2011; van den Boogaard et al., 2012; Mostowska et al., 2013; Plaisancie et al., 2013; Tardieu et al., 2017); Case control studies suggest this variant is associated with hypodontia (van den Boogaard et al., 2012); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 21484994, 20301291, 23401279, 22581971, 24700731, 23167694, 24398796, 24123366, 25333069, 21228398, 24702986, 23991204, 25629078, 19559398, 28105635, 20979233, 27881089, 26049155, 25545742, 26087098, 28813618, 28976000, 29364747, 29364501, 29431110, 24449199, 21279306, 30046887, 30426266, 31798653, 32618450, 31618753, 33144682) -

Tooth agenesis, selective, 4

Pathogenic:5

Likely pathogenic, criteria provided, single submitter	clinical testing	Undiagnosed Diseases Network, NIH	Mar 12, 2018	- -
Pathogenic, criteria provided, single submitter	clinical testing	MGZ Medical Genetics Center	Jun 13, 2022	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Feb 01, 2014	- -
Likely pathogenic, criteria provided, single submitter	clinical testing	Genetics and Molecular Pathology, SA Pathology	May 12, 2021	The WNT10A c.682T>A variant is classified as LIKELY PATHOGENIC (low penetrance) (PP3, PS3, PS4) The WNT10A c.682T>A variant is a single nucleotide change in exon 3 of the WNT10A gene, which is predicted to change the amino acid phenylalanine at position 228 in the protein to isoleucine. This variant has been reported in a heterozygous state in many individuals with isolated hypodontia or oligodontia, as well as in unaffected carriers and is therefore considered to be a pathogenic variant with low penetrance. Although the population frequency is high (approximately 1.37%), the incidence of this dental agenesis is significantly higher (approximately 6.75%) (PMID:25713620) (PS4). Large meta analysis shows 2.25 - 3.42 fold increased risk for isolated tooth agenesis (PMID:29364747) (PS3). This variant has conflicting reports of pathogenicity in ClinVar, although the majority of other diagnostic laboratories classify it as pathogenic (ClinVar Variation ID: 19501). This variant has been reported as damaging in HGMD (CM094237). Computational predictions support a deleterious effect on the gene or gene product (PP3). -
Pathogenic, criteria provided, single submitter	clinical testing	DASA	Feb 14, 2022	The c.682T>A;p.(Phe228Ile) missense variant has been observed in affected individual(s) (PMID: 30974434; 30426266; 29364747; 28976000; 28813618; 27881089; 24700731; 22581971; 21279306; 20979233; 21484994) - PS4.The p.(Phe228Ile) was detected in trans with a pathogenic variant (PMID: 30426266; 28976000; 28813618; 24700731; 22581971; 21279306; 20979233; 21484994) - PM3_strong. The variant co-segregated with disease in multiple affected family members (PMID: 30426266; 24700731; 21279306; 20979233; 21484994) - PP1_strong. Multiple lines of computational evidence support a deleterious effect on the gene or gene product - PP3 and allele frequency is greater than expected for disorder - BS1. In summary, the currently available evidence indicates that the variant is pathogenic. -

Odonto-onycho-dermal dysplasia

Pathogenic:3Uncertain:1

Pathogenic, no assertion criteria provided	literature only	OMIM	Feb 01, 2014	- -
Pathogenic, criteria provided, single submitter	clinical testing	Johns Hopkins Genomics, Johns Hopkins University	Apr 12, 2023	- -
Pathogenic, criteria provided, single submitter	clinical testing	Mendelics	May 27, 2022	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jun 10, 2021	- -

Odonto-onycho-dermal dysplasia;C1835492:Tooth agenesis, selective, 4;C1857069:SchC6pf-Schulz-Passarge syndrome

Pathogenic:1Other:2

not provided, no classification provided	phenotyping only	GenomeConnect - Invitae Patient Insights Network	-	Variant interpreted as Pathogenic and reported on 01-00-1900 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. -
not provided, no classification provided	phenotyping only	GenomeConnect - Brain Gene Registry	-	Variant classified as Pathogenic and reported on 02-18-2020 by GeneDx. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/. -
Pathogenic, criteria provided, single submitter	clinical testing	New York Genome Center	Mar 22, 2023	- -

Hypohidrotic ectodermal dysplasia

Pathogenic:2

Pathogenic, criteria provided, single submitter	clinical testing	Breda Genetics srl	Aug 29, 2016	This variant has been identified in an individual with congenital alopecia, hypodontia, and hypohidrosis. In the family, inheritance was compatible with a dominant pattern. This nonsynonymous variant is reported with an estimated allele frequency of 0.014 in gnomAD exomes, 0.01215 in gnomAD genomes, and 0.019 in NHLI Exome Sequencing Project (ESP). The nucleotide position is conserved across 35 mammalian species (GERP RS: 4.46). In silico analysis indicates that the variant might be damaging (MutationTaster: disease-causing; FATHMM-MKL: damaging; Provean: damaging; DANN: 0.992). The p.Phe228Ile mutation represents the most common allele identified in cases with isolated hypodontia (PMIDs: 22581971, 24449199, 24700731). Reduced penetrance and variable expressivity have been reported in carriers of the p.Phe228Ile mutation. Nearly half of heterozygotes may display mild multifocal symptoms, such as variable abnormalities of skin, hair, teeth or nails (PMIDs: 19559398, 21279306). For instance, van den Boogaard et al. (PMID: 22581971) reported a p.Phe228Ile heterozygote presenting with hypodontia, alopecia, hypohidrosis and mild nail dysplasia. Autosomal dominant inheritance of isolated hypodontia-microdontia in p.Phe228Ile heterozygotes has been described also by Kantaputra and Sripathomsawat (PMID: 21484994). -
Pathogenic, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Sep 12, 2023	The p.Phe228Ile variant in WNT10A has been reported in over 50 individuals with clinical features of ectodermal dysplasia or isolated tooth agenesis (hypodontia) in the homozygous or compound heterozygous state. It has also been seen in the heterozygous state in individuals with tooth agenesis with or without some features of ectodermal dysplasia as well as in asymptomatic family members. This variant segregated with disease in at least 17 affected individuals from multiple families (Bohring 2009 PMID: 19559398, Kantaputra 2011 PMID: 21484994, van den Boogaard 2012 PMID: 22581971, Mostowska 2013 PMID: 23167694, Plaisancie 2013 PMID: 23401279, Arzoo 2013 PMID: 24449199, Mues 2014 PMID: 24700731). This variant has also been reported by other clinical laboratories in ClinVar (Variation ID 4462) and has been identified in 3.5% (120/3470) of Ashkenazi Jewish and 2.2% (1515/67998) of European chromosomes, including many homozygotes by gnomAD (http://gnomad.broadinstitute.org, v.3.1.2). However, studies have consistently found that it is in a significantly higher proportion of tooth agenesis cohorts than control cohorts (Bohring 2009 PMID: 19559398, Arzoo 2013 PMID: 24449199, Mues 2014 PMID: 24700731). In a large meta-analysis, this variant was associated with a 2.25-3.42-fold risk (95% CI: 1.39-4.10) for isolated tooth agenesis, the autosomal dominant condition associated with WNT10A (Jonsson 2018 PMID: 29364747). This variant is thought to have lower penetrance with variable expressivity, as heterozygotes for this variant were either asymptomatic or had hypodontia and/or mild clinical features of ectodermal dysplasia (Bohring 2009 PMID: 19559398). Computational prediction tools and conservation analyses suggest that this variant may impact the protein. In summary, this variant meets criteria to be classified as pathogenic for clinical features of ectodermal dysplasia, ranging from isolated tooth agenesis with or without other clinical features in the heterozygous state to a classic ectodermal dysplasia phenotype in the homozygous or compound heterozygous state. However, this variant is associated with a lower penetrant disease compared to other pathogenic variants in the WNT10A gene. ACMG/AMP Criteria applied: PM3_VeryStrong, PP1_Strong, PP3. -

Ectodermal dysplasia

Pathogenic:1Other:1

Pathogenic, criteria provided, single submitter	research	Division of Human Genetics, National Health Laboratory Service/University of the Witwatersrand	Jul 01, 2023	- -
not provided, no classification provided	literature only	GeneReviews	-	- -

Inborn genetic diseases

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 25, 2024

The c.682T>A (p.F228I) alteration is located in coding exon 3 of the WNT10A gene. This alteration results from a T to A substitution at nucleotide position 682, causing the phenylalanine (F) at amino acid position 228 to be replaced by an isoleucine (I). Based on data from gnomAD, the A allele has an overall frequency of 1.372% (3770/274884) total alleles studied. The highest observed frequency was 3.482% (359/10310) of Ashkenazi Jewish alleles. The p.F228I alteration is often associated with a severe ectodermal dysplasia phenotype when occurring in the homozygous or compound heterozygous state with other pathogenic alterations (Bohring, 2009; Plaisancié, 2013; Reuter, 2018; Guazzarotti, 2018; Ruiz-Heiland, 2019). A genome-wide association study (GWAS) found a significant association between this alteration and tooth agenesis (p-value=5.2 x 10-6; odds ratio for heteterozygotes = 3.0; odds ratio for homozygotes = 51.3; Jonsson, 2018). Individuals who are heterozygous for the p.F228I alteration may have a mild phenotype including dental anomalies and palmar/plantar hyperkeratosis, though penetrance is incomplete and expression is variable (Bohring, 2009; Guazzarotti, 2018; Ruiz-Heiland, 2019). This amino acid position is highly conserved in available vertebrate species. This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic. -

Tooth agenesis

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

Yale Center for Mendelian Genomics, Yale University

Sep 15, 2014

- -

See cases

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Institute of Human Genetics, University Hospital Muenster

Jan 17, 2017

ACMG categories: PS4,PS5,PP3,PP4,PP5 -

WNT10A-related disorder

Pathogenic:1

Pathogenic, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 23, 2024

The WNT10A c.682T>A variant is predicted to result in the amino acid substitution p.Phe228Ile. This variant has been reported in the heterozygous and compound heterozygous states as the most common variant found in patients affected with taurodontism, non-syndromic missing teeth, or mild ectodermal dysplasia (Vink et al. 2014. PubMed ID: 24398796; Yang et al. 2015. PubMed ID: 25629078; Arzoo et al. 2014. PubMed ID: 24449199; Bergendal et al. 2016. PubMed ID: 27881089; Guazzarotti et al. 2018. PubMed ID: 28976000). However, this variant was also observed in a genomic variant database with minor allele frequencies ranging from 0% to ~3.5%, with >40 homozygotes listed. Incomplete penetrance has been documented for this variant (Yang et al. 2015. PubMed ID: 25629078). Based on this evidence, this variant is interpreted as pathogenic. -

Odonto-onycho-dermal dysplasia;C1835492:Tooth agenesis, selective, 4

Pathogenic:1

Pathogenic, low penetrance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

This sequence change replaces phenylalanine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 228 of the WNT10A protein (p.Phe228Ile). This variant is present in population databases (rs121908120, gnomAD 3%), including at least one homozygous and/or hemizygous individual. This variant has been observed in many individuals with autosomal recessive forms of ectodermal dysplasia (PMID: 19559398, 28976000, 30974434, Invitae). It has been found in trans (on the opposite chromosome) from many different pathogenic variants. Based on an internal analysis, this variant is associated with reduced penetrance for autosomal recessive disease (15% when in homozygosity and 30-60% when present with another pathogenic variant) compared to other pathogenic or likely pathogenic variants, which have a penetrance of 70-80% (Invitae). In addition, in a large meta-analysis, this variant conferred a 2.25-3.42-fold increased risk (95% CI: 1.39-4.10) for isolated tooth agenesis, the autosomal dominant condition associated with WNT10A (PMID: 29364747). ClinVar contains an entry for this variant (Variation ID: 4462). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt WNT10A protein function with a positive predictive value of 80%. In summary, this variant is reported to cause disease. However, because this variant is associated with a lower penetrance form of disease than other pathogenic alleles in the WNT10A gene, and because it is found in homozygosity in healthy individuals, it has been classified as Pathogenic (low penetrance). -

Tooth agenesis, selective, 4;C1857069:SchC6pf-Schulz-Passarge syndrome

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

Aug 27, 2021

PM3_Strong, PP1, PP3 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Benign

-0.033

BayesDel_noAF

Pathogenic

0.20

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.89

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

MetaRNN

Benign

0.014

MetaSVM

Uncertain

0.41

MutationAssessor

Pathogenic

3.4

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.79

PROVEAN

Pathogenic

-5.0

REVEL

Pathogenic

0.86

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.35

MPC

0.50

ClinPred

0.060

GERP RS

4.5

Varity_R

0.87

gMVP

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over